Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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Research Abstract |
Recent advances in high-resolution computed tomography (HRCT) imaging have led to the increased detection rate of small lung tumors, especially bronchioloalveolar carcinoma (BAC) and atypical adenomatous hyperplasia (AAH). AAH is considered to be a preinvasive lesion of BAC. HRCT of AAH or BAC tumors exhibits the focal area of ground-glass opacity which corresponds to abronchioloalveolar replacement pattern by tumor cells. Recently, it has been reported by us or others that BAC or AAH may arise as multifocal lesions. Appropriate treatment for such multifocal BAC remains controversial, but several studies have shown successful resection using video-assisted thoracoscopic surgery. However, the precise pathogenesis or the mechanism of tumorigenesis of such spatial multiplicity and temporal synchronicity remains undetermined. First, we reported two cases of multiple BACs associated with acromegaly whose serum levels of insulin-like growth factor I (IGF-I) were elevated. In this regard, immun
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ohistochemical examination of tumors resected from these two cases demonstrated positive staining for IGF-I receptor (IGF-IR), a specific cell-membrane receptor for IGF-I. Since IGF-I is a member of peptide growth factors with a property of regulating cell proliferation and differentiation, and IGF-IR is known as a positive regulator of cell survival and growth of lung cancer cells, the IGF-I and IGF-IR system may be playing a role in tumorigenesis of multifocal BACs. Second, we have analyzed mRNA expression profiling in 17 surgically-resected lung cancer specimens, mainly BACs, of 8 patients by using Affymetrix's GeneChip Human Genome U133 Plus 2.0 Array. In 2 well-reserved and comparable sets of lung cancer specimens, mRNA transcripts which were downregulated in both cancer tissues included metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), and so on. In contrast, transcripts which were upregulated in both cancer tissues were those of matrix metallopeptidase 7, ATP-binding cassette sub-family C member 3, or CD24. In conclusion, it is likely that common molecular mechanisms would be responsible for such spatially and temporally synchronous oncogenesis in multiple lung adenocarcinomas. Less
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